Infección cónica por el virus de la Hepatitis B: Rol de la interacción entre la respuesta inmune intrahepática y el virus en el contexto de la injuria hepática

GIADANS C; FRÍAS S.; PIETRANATONIO A; GALDAME O; FLICHMAN D; AMEIGEIRAS B; RÍOS D; ROMEO JM; HADAD L; VISTARINI C; DE MATTEO E; LUCATELLI N; M V PRECIADO; MULLEN E; VALVA P

Congreso; 18th International Congress on Infectious Diseases (ICID) y XVIII Congreso de SADI; 2018

Chronic hepatitis B virus (HBV) infection is still a global health problem. Even though it is well known that adaptative immune response plays an important role in the pathogenesis of chronic infection, the impact of each immune cell population on liver damage and viral surveillance is still a matter of debate.Our aim was to elucidate the interplay between the immune response and viral activity in the context of liver damage. Immunostaining was performed in 23 liver biopsies from CHB treatment naïve patients (40% HBeAg-positive) to: 1) characterize liver infiltrate [Th (CD4+), Th1 (Tbet+), Th17 (IL-17A+), Treg (Foxp3+), and CTL (CD8+)] [portal quantification: immunostained/total lymphocytes; lobular quantification: immunostained lymphocytes in 10 fields; (400x)], 2) evaluate the Hepatitis B surface antigen (HBsAg) expression (presence was determined). Inflammatory activity and fibrosis were assessed using the modified Knodell scoring system (Histological Activity Index, HAI) and METAVIR. All studied populations were observed in portal/periportal infiltrates with predominance of Th {Th [0.65 (0.33-0.77)] > CTL [0.54 (0.16-0.74)] > Treg [0.09 (0.00-0.25)] > Th1 [0.07 (0-0.20)] > Th17 [0.05 (0-0.20)]}. However, only CTL were present in the intralobular area [2.77 (0.01-0.25)]. Concerning liver damage, Th17 frequency was increased in cases with more severe fibrosis (p=0.04), while Th in cases with severe hepatitis (p=0.02) mostly due to Treg (p=0.02). The frequency of intralobular CTL also depicted association with severe hepatitis (p=0.02). Regarding HBV antigen profile, only 62% of cases showed presence of HBsAg, being its absence associated with a higher number of Treg (p=0.02) and severe hepatitis (p=0.01). Moreover, HBe Ag-positive cases exhibited higher Treg and Th frequencies (p=0.0002 and p=0.037; respectively). Although Treg population was highly represented in the infiltrate, they were not related to liver damage. In contrast, intrahepatic Th17 mediated fibrosis severity. The presence of CTL in the intralobular area may indicate a relationship between them and hepatocytes denoting their contribution to hepatitis severity. Finally, our results suggest that the presence of a regulatory microenvironment enhances viral replication. This hypothesis is supported by the fact that a higher Treg frequency was observed in the context of absence HBsAg as well as among HBeAg-positive cases.